Plasma mitochondrial DNA as a biomarker of disease progression in idiopathic pulmonary fibrosis

Introduction: Plasma mitochondrial DNA (mtDNA) is known as a predictor of all-cause mortality in idiopathic pulmonary fibrosis (IPF) patients. However, the relationship between plasma mtDNA and disease progression in IPF are not well defined. Aims: To investigate the role of plasma mtDNA as a biomarker for disease progression in IPF. Methods: Clinical data and plasma mtDNA levels at diagnosis were retrospectively analyzed in 363 IPF patients (mean age: 64.0 years, male: 78.5%). Plasma mtDNA was measured by real-time polymerase chain reaction and expressed as a copy number of the human nicotinamide adenine dinucleotide reduced (NADH) dehydrogenase 1 gene. Disease progression was defined as ≥ 10% decline in forced vital capacity (FVC) at six months Results: Median follow-up period was 45.8 months. The baseline levels of mtDNA showed significant correlation with body mass index (r=0.114, P=0.044), diffusing capacity (DLco) (r=0.203, P<0.001), the lowest oxygen saturation during 6-minute walk test (r=-0.139, P=0.015), and decline in FVC (r=-0.135, P=0.040) and DLco (r=-0.224, P<0.001) at six months. Disease progression was identified in 16.7% of 252 patients who have lung function data at 6 months. Progressed group showed a higher level of mtDNA than non-progressed group (249.9 vs. 145.3 copies/uL, P=0.038). Following covariates adjustments for age, sex, smoking, FVC and DLco (% predicted), the elevated mtDNA level (≥33.7 copies/uL) was an only independent predictor for disease progression in multivariate analysis (odds ratio, 2.006; 95% CI, 1.007-3.998; P=0.048). Conclusions: Our finding suggest that plasma mtDNA could be useful for predicting disease progression in IPF.